The Global Burden of Liver Disease

Chronic liver disease (CLD) and its associated complications (cirrhosis and liver cancer) cause significant mortality, morbidity, and economic burden. Published data from the World Health Organization and/or the Global Burden of Disease show that the burden of CLD is large and increasing, primarily owing to the increasing burden of nonalcoholic fatty liver disease and alcohol-related liver disease (ALD). Middle Eastern, Northern African, and Asian regions of the globe are most affected by hepatitis B and hepatitis C virus. Furthermore, Middle Eastern and North African regions also are affected by nonalcoholic fatty liver disease, and Eastern European, West African, and Central Asian regions are affected by ALD. In this context, the rate of increase for cirrhosis is highest in the Middle East, as well as in middle high and high sociodemographic index (SDI) regions. On the other hand, the highest SDI countries are experiencing increasing rates of hepatocellular carcinoma (HCC). Assessing HCC burden based on country and etiology shows that China, Korea, India, Japan, and Thailand have the highest hepatitis B virus–related HCC cases, while China, Japan, and the United States have the highest hepatitis C virus–related HCC cases. Additionally, the United States has the highest ALD-related HCC cases, while India, the United States, and Thailand have the highest nonalcoholic steatohepatitis–related HCC cases. Although the burden of CLD is increasing globally, regions of the world are impacted differently as a result of a number of sociodemographic factors. Chronic liver disease (CLD) and its associated complications (cirrhosis and liver cancer) cause significant mortality, morbidity, and economic burden. Published data from the World Health Organization and/or the Global Burden of Disease show that the burden of CLD is large and increasing, primarily owing to the increasing burden of nonalcoholic fatty liver disease and alcohol-related liver disease (ALD). Middle Eastern, Northern African, and Asian regions of the globe are most affected by hepatitis B and hepatitis C virus. Furthermore, Middle Eastern and North African regions also are affected by nonalcoholic fatty liver disease, and Eastern European, West African, and Central Asian regions are affected by ALD. In this context, the rate of increase for cirrhosis is highest in the Middle East, as well as in middle high and high sociodemographic index (SDI) regions. On the other hand, the highest SDI countries are experiencing increasing rates of hepatocellular carcinoma (HCC). Assessing HCC burden based on country and etiology shows that China, Korea, India, Japan, and Thailand have the highest hepatitis B virus–related HCC cases, while China, Japan, and the United States have the highest hepatitis C virus–related HCC cases. Additionally, the United States has the highest ALD-related HCC cases, while India, the United States, and Thailand have the highest nonalcoholic steatohepatitis–related HCC cases. Although the burden of CLD is increasing globally, regions of the world are impacted differently as a result of a number of sociodemographic factors. Chronic liver disease (CLD) and associated cirrhosis accounts for approximately 1 million deaths per year. In addition to its clinical burden, CLD causes significant morbidity, impairment of health-related quality of life (HRQL), and economic burden.1Asrani S.K. Devarbhavi H. Eaton J. Kamath P.S. Burden of liver diseases in the world.J Hepatol. 2019; 70: 151-171Abstract Full Text Full Text PDF PubMed Scopus (1522) Google Scholar Although there are a number of causes of liver disease, the 4 major drivers of this CLD-related burden include chronic hepatitis C virus (CHC), chronic hepatitis B virus (CHB), alcohol-related liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). In fact, given the pandemic of obesity, its associated liver disease, NAFLD, is increasing and is predicted to continue to do so.2Paik J.M. Golabi P. Younossi Y. et al.Changes in the global burden of chronic liver diseases from 2012 to 2017: the growing impact of NAFLD.Hepatology. 2020; 72: 1605-1616Crossref PubMed Scopus (272) Google Scholar, 3Estes C. Anstee Q.M. Arias-Loste M.T. et al.Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.J Hepatol. 2018; 69: 896-904Abstract Full Text Full Text PDF PubMed Scopus (876) Google Scholar, 4Estes C. Razavi H. Loomba R. et al.Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.Hepatology. 2018; 67: 123-133Crossref PubMed Scopus (1108) Google Scholar, 5Estes C. Chan H.L.Y. Chien R.N. et al.Modelling NAFLD disease burden in four Asian regions-2019-2030.Aliment Pharmacol Ther. 2020; 51: 801-811Crossref PubMed Scopus (66) Google Scholar, 6World Health OrganizationEstimated mortality rate from cirrhosis and other chronic liver diseases.https://www.who.int/data/gho/indicator-metadata-registry/imr-details/1179Date accessed: December 13, 2022Google Scholar, 7World Health Statistics.file:///C:/Users/User/Downloads/9789240051140-eng.pdfDate accessed: December 13, 2022Google Scholar, 8Rehm J. Gmel Sr., G.E. Gmel G. et al.The relationship between different dimensions of alcohol use and the burden of disease-an update.Addiction. 2017; 112: 968-1001Crossref PubMed Scopus (593) Google Scholar, 9Rehm J. Imtiaz S. A narrative review of alcohol consumption as a risk factor for global burden of disease.Subst Abuse Treat Prev Policy. 2016; 11: 37Crossref PubMed Scopus (105) Google Scholar, 10Messina J.P. Humphreys I. Flaxman A. et al.Global distribution and prevalence of hepatitis C virus genotypes.Hepatology. 2015; 61: 77-87Crossref PubMed Scopus (1173) Google Scholar, 11Schwarzinger M. Baillot S. Yazdanpanah Y. et al.Alcohol use disorders and the burden of chronic hepatitis C in France, 2008-2013: a nationwide retrospective cohort study.J Hepatol. 2017; 67: 454-461Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 12Rehm J. Shield K.D. Global burden of alcohol use disorders and alcohol liver disease.Biomedicines. 2019; 7: 99Crossref PubMed Scopus (69) Google Scholar, 13Younossi Z. Golabi P. Paik J.M. et al.The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): a systematic review and meta-analysis.Hepatology. 2023; 77: 1335-1347Crossref PubMed Scopus (18) Google Scholar Given the potentially changing landscape of CLD is necessary for local, regional, and global policy makers to deal with this important disease. This review provides an overview of the current burden and future trends related to 4 major causes of CLD from a global perspective. Currently, the World Health Organization (WHO) estimates that 58 million people have CHC, with approximately 1.5 million new infections and approximately 300,000 annual deaths (Table 1).6World Health OrganizationEstimated mortality rate from cirrhosis and other chronic liver diseases.https://www.who.int/data/gho/indicator-metadata-registry/imr-details/1179Date accessed: December 13, 2022Google Scholar,7World Health Statistics.file:///C:/Users/User/Downloads/9789240051140-eng.pdfDate accessed: December 13, 2022Google Scholar Furthermore, it is estimated that 3.2 million adolescents and children are infected with CHC. The highest burden of CHC is found in the Eastern Mediterranean and European regions, followed by South-East Asia, the Western Pacific, Africa, and the Americas.6World Health OrganizationEstimated mortality rate from cirrhosis and other chronic liver diseases.https://www.who.int/data/gho/indicator-metadata-registry/imr-details/1179Date accessed: December 13, 2022Google Scholar,7World Health Statistics.file:///C:/Users/User/Downloads/9789240051140-eng.pdfDate accessed: December 13, 2022Google ScholarTable 1Chronic Liver Disease Prevalence Rates by Global Organization (2019)Chronic liver diseaseWHOGBDPolaris ObservatoryHepatitis B virus296 million infected820,000 annual deaths1.5 million new infections10% diagnosed2% treatedAreas most affected: Western Pacific, Africa, Southeast Asia, Eastern Mediterranean316 million infected555,000 annual deathsAreas most affected: Africa and Burma2.91 million infected (2016)10% diagnosed8% treatedAreas most affected: Africa, Western PacificHepatitis C virus58 million infected (3.2 million children)300,000 annual deaths1.5 million new infections21% diagnosed13% treatedAreas most affected: Eastern Mediterranean, Europe, South East Asia, Western Pacific, Africa, regions of the Americas113 million infected (58.8 million females, 54.4 million males)500,000 annual deaths82.5 new cases per 100,000 people9.4 million people treated from 2015–2019Areas most affected: Asia and Africa56.8 million infected1.42 million new infections until 20302.3% diagnosed5% treatedAreas most affected: Eastern Europe, Asia (Central and Southeast)Nonalcoholic fatty liver diseaseNot recognized by the WHO as a priority among noncommunicable diseases1,235.7 million are estimated to have NAFLD (all ages)1.75–2.18 per 100,000 all age death rateAreas most affected: Middle East and North Africa regions; by country: China, India, and IndonesiaCentral Latin America had highest death rate at 5.9 per 100,000 personsNot applicableALDReports burden of ALD through mortality and disability-adjusted life yearsMortality (2016): 588,000 liver deaths accounting for 46.9% of all liver deathsCountries with highest disability-adjusted life years: Eastern Europe, West Africa, Central AsiaBecause of lack of accurate reporting and referral bias GBD does not report incidence or prevalence but reports mortality:27% of deaths from liver disease30% of liver cancer deathsBurden of ALD is dispersed worldwide, top 5 countries/regions (2019): Mongolia, Kazakhstan, El Salvador, Guatemala, GreenlandNot applicableALD, alcohol-related liver disease; GBD, Global Burden of Disease; WHO, World Health Organization.Data from Spearman et al,14Spearman W.C. Dusheiko G.M. Hellard M. Sonderup M. Hepatitis C.Lancet. 2019; 394: 1451-1466Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar WHO,15WHO. Global health sector strategy on viral hepatitis 2016–2021. Towards ending viral hepatitis. World Health Organization, Geneva, Switzerland2016Google Scholar Polaris Observatory HCV Collaborators,16Polaris Observatory HCV CollaboratorsGlobal change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.Lancet Gastroenterol Hepatol. 2022; 7: 396-415Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar and Polaris Observatory Collaborators.17Polaris Observatory CollaboratorsGlobal prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.Lancet Gastroenterol Hepatol. 2018; 3: 383-403Abstract Full Text Full Text PDF PubMed Scopus (1051) Google Scholar Open table in a new tab ALD, alcohol-related liver disease; GBD, Global Burden of Disease; WHO, World Health Organization. Data from Spearman et al,14Spearman W.C. Dusheiko G.M. Hellard M. Sonderup M. Hepatitis C.Lancet. 2019; 394: 1451-1466Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar WHO,15WHO. Global health sector strategy on viral hepatitis 2016–2021. Towards ending viral hepatitis. World Health Organization, Geneva, Switzerland2016Google Scholar Polaris Observatory HCV Collaborators,16Polaris Observatory HCV CollaboratorsGlobal change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.Lancet Gastroenterol Hepatol. 2022; 7: 396-415Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar and Polaris Observatory Collaborators.17Polaris Observatory CollaboratorsGlobal prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.Lancet Gastroenterol Hepatol. 2018; 3: 383-403Abstract Full Text Full Text PDF PubMed Scopus (1051) Google Scholar In addition to the WHO, the disease burden data for CLD can be obtained from the global burden of disease (GBD). The Institute for Health Metrics and Evaluation (IHME), an independent global health research center located at the University of Washington, is responsible for coordinating the GBD research and database.18Institute for Health Metrics and Evaluation (IHME).https://www.healthdata.orgDate accessed: December 13, 2022Google Scholar The purpose of IHME and GBD research is to provide health trend data over time to local, regional, national, and international health care policy makers so that appropriate interventions can be developed. To accomplish this, the IHME conducts global research in more than 195 countries.18Institute for Health Metrics and Evaluation (IHME).https://www.healthdata.orgDate accessed: December 13, 2022Google Scholar Because of the methodology that GBD investigators use to conduct their vast research, regular updates allow for comparison of outcomes over time.19IHME updates.https://www.healthdata.org/gbd/about#:∼:text=GBD%20research%20incorporates%20both%20the,use%20that%20information%20at%20homeDate accessed: December 13, 2022Google Scholar As such, GBD researchers recently released several reports that are relevant to the global burden of CLD.18Institute for Health Metrics and Evaluation (IHME).https://www.healthdata.orgDate accessed: December 13, 2022Google Scholar,19IHME updates.https://www.healthdata.org/gbd/about#:∼:text=GBD%20research%20incorporates%20both%20the,use%20that%20information%20at%20homeDate accessed: December 13, 2022Google Scholar The global impact of CHC using GBD data has been quantified in a summary report compiled by the global health metrics team.14Spearman W.C. Dusheiko G.M. Hellard M. Sonderup M. Hepatitis C.Lancet. 2019; 394: 1451-1466Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar The GBD estimated that the total prevalence of hepatitis C virus (HCV) in 2019 was 113 million cases, with females accounting for 58.8 million and males for 54.4 million cases. There were half a million deaths related to CHC, with males accounting for 64% of the deaths. The incidence rate for HCV was reported at 82.5 cases per 100,000 people.14Spearman W.C. Dusheiko G.M. Hellard M. Sonderup M. Hepatitis C.Lancet. 2019; 394: 1451-1466Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar Despite the availability of curative regimens for HCV since 2013,20Tordrup D. Hutin Y. Stenberg K. et al.Cost-effectiveness of testing and treatment for hepatitis B virus and hepatitis C virus infections: an analysis by scenarios, regions, and income.Value Health. 2020; 23: 1552-1560Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, 21Tordrup D. Hutin Y. Stenberg K. et al.Additional resource needs for viral hepatitis elimination through universal health coverage: projections in 67 low-income and middle-income countries, 2016-30.Lancet Glob Health. 2019; 7: e1180-e1188Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 22Yousafzai M.T. Bajis S. Alavi M. et al.Global cascade of care for chronic hepatitis C virus infection: a systematic review and meta-analysis.J Viral Hepat. 2021; 28: 1340-1354Crossref PubMed Scopus (16) Google Scholar, 23Zoratti M.J. Siddiqua A. Morassut R.E. et al.Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: a systematic literature review and meta-analysis.EClinicalMedicine. 2020; 18100237Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 24Pecoraro V. Banzi R. Cariani E. et al.New direct-acting antivirals for the treatment of patients with hepatitis C virus infection: a systematic review of randomized controlled trials.J Clin Exp Hepatol. 2019; 9: 522-538Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar HCV remained (in 2019) the 23rd leading cause of death, the 25th cause for years of life lost, the 123rd cause for years of life disability, and the 41st cause for disability life-adjusted years (DALYs). A large proportion of DALYs related to HCV are accounted for by the presence of cirrhosis.20Tordrup D. Hutin Y. Stenberg K. et al.Cost-effectiveness of testing and treatment for hepatitis B virus and hepatitis C virus infections: an analysis by scenarios, regions, and income.Value Health. 2020; 23: 1552-1560Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar In other analyses of GBD 2019 data, Asian and African regions had the highest prevalence of CHC, for which the top countries included Mongolia, Cambodia, Chad, Uzbekistan, Gabon, Democratic Republic of the Congo, Central African Republic, Angola, Turkmenistan, Tajikistan, and Kyrgyzstan (Figure 1A). Understanding the regional burden of CHC allows for targeted efforts to target countries with the highest burden for long-term and sustainable programs to eradicate CHC. These challenges are immense given the fact that current data suggest that only 13% of eligible patients have received treatment and 78.6% of HCV infections remain undiagnosed.25Cui F. Blach S. Manzengo Mingiedi C. et al.Global reporting of progress towards elimination of hepatitis B and hepatitis C.Lancet Gastroenterol Hepatol. 2023; 8: 332-342Abstract Full Text Full Text PDF PubMed Google Scholar,26Le L.V. Blach S. Rewari B. et al.Progress towards achieving viral hepatitis B and C elimination in the Asia and Pacific region: results from modelling and global reporting.Liver Int. 2022; 42: 1930-1934Crossref PubMed Scopus (6) Google Scholar In addition, only 11 countries are currently on track to eliminate hepatitis by 2030, and the 5 countries with the highest burden of HCV may not reach the elimination goals until 2050.15WHO. Global health sector strategy on viral hepatitis 2016–2021. Towards ending viral hepatitis. World Health Organization, Geneva, Switzerland2016Google Scholar,27Blach S. Razavi-Shearer D. Mooneyhan E. et al.Updated evaluation of global progress towards HBV and HCV elimination, preliminary data through 2021. 76. 2022: S1-S1564Google Scholar In addition to WHO and GBD, the Polaris Observatory HCV Collaborators (a global initiative to eliminate hepatitis) recently provided an updated report on the status of CHC.16Polaris Observatory HCV CollaboratorsGlobal change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.Lancet Gastroenterol Hepatol. 2022; 7: 396-415Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar They have estimated that there were 56.8 million people living with HCV at the beginning of 2020. According to their estimates, Eastern Europe (2.9%; 95% uncertainty interval [UI], 2.3–3.2) and Central Asia (2.6%; 95% UI, 2.4–2.8) have the highest prevalence of HCV, while the largest number of cases of HCV-infected individuals is seen in South Asia (14.0 million; 95% UI, 13.2–24.2) and East Asia (10.0 million; 95% UI, 8.6–11.9). It is anticipated that an average of 1.42 million new infections will occur each year until the end of 2030. By 2030, liver-related outcomes of HCV (liver-related deaths, hepatocellular carcinoma, and decompensated cirrhosis) are projected to increase by 14% to 17%. This increase could offset any improvement expected from treating HCV-infected patients. Finally, these investigators determined that only 23% of those with CHC have been diagnosed and only 5% have received treatment, indicating significant gaps in the HCV elimination strategy.16Polaris Observatory HCV CollaboratorsGlobal change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.Lancet Gastroenterol Hepatol. 2022; 7: 396-415Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar The WHO estimates that 296 million people were living with CHB infection in 2019. Another 1.5 million new infections and an estimated 820,000 deaths (mostly owing to cirrhosis and hepatocellular carcinoma) were expected.6World Health OrganizationEstimated mortality rate from cirrhosis and other chronic liver diseases.https://www.who.int/data/gho/indicator-metadata-registry/imr-details/1179Date accessed: December 13, 2022Google Scholar,7World Health Statistics.file:///C:/Users/User/Downloads/9789240051140-eng.pdfDate accessed: December 13, 2022Google Scholar The burden of CHB is highest in the Western Pacific, followed by Africa, as well as the Eastern Mediterranean, South-East Asia, Europe, and the Americas.6World Health OrganizationEstimated mortality rate from cirrhosis and other chronic liver diseases.https://www.who.int/data/gho/indicator-metadata-registry/imr-details/1179Date accessed: December 13, 2022Google Scholar,7World Health Statistics.file:///C:/Users/User/Downloads/9789240051140-eng.pdfDate accessed: December 13, 2022Google Scholar The GBD estimates the global CHB prevalence (2019) at 4.1% (3.7%–4.5%), corresponding to 316 million (95% UI: 284–351 million) cases of hepatitis B virus (HBV)-infected individuals.28GBD 2019 Hepatitis B CollaboratorsGlobal, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet Gastroenterol Hepatol. 2022; 7: 796-829Abstract Full Text Full Text PDF PubMed Google Scholar The GBD also estimates that in 2019 there were 555,000 (95% UI: 487,000–630,000) CHB-related deaths.28GBD 2019 Hepatitis B CollaboratorsGlobal, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet Gastroenterol Hepatol. 2022; 7: 796-829Abstract Full Text Full Text PDF PubMed Google Scholar,29Paik J.M. Younossi Y. Henry L. et al.Recent trends in the global burden of hepatitis B virus: 2007-2017.Gastroenterology. 2021; 160: 1845-1846.e3Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Interestingly, it was noted that there has been a 31.3% (95% UI: 29.0%–33.9%) decrease in the prevalence of CHB between 1990 and 2019. This decrease was most notable among children younger than 5 years (76.8%; 95% UI: 76.2%–77.5% decrease).29Paik J.M. Younossi Y. Henry L. et al.Recent trends in the global burden of hepatitis B virus: 2007-2017.Gastroenterology. 2021; 160: 1845-1846.e3Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Despite this decrease in prevalence, death rates are continuing to increase in many countries. This conundrum may be owing to the aging of the population as well as that more time is needed to determine whether the decreasing prevalence rates can translate into a reduction in mortality.30Sohn E. The global fight against hepatitis B is benefitting some parts of the world more than others.Nature. 2022; 603: S58-S59Crossref PubMed Google Scholar, 31Tian F. Feld J.J. Feng Z. et al.Feasibility of hepatitis B elimination in high-income countries with ongoing immigration.J Hepatol. 2022; 77: 947-956Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 32Stockdale A.J. Meiring J.E. Shawa I.T. et al.Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi.J Infect Dis. 2022; 226: 871-880Crossref PubMed Scopus (3) Google Scholar Similar to CHC, Africa had the largest burden of CHB, for which the top countries included Burkina Faso, Mauritania, Guinea, Guinea-Bissau, Chad, Angola, Ghana, Mozambique, Somalia, Malawi, and Niger (Figure 1B). The Polaris Observatory Hepatitis B Collaborators also have produced a modeling report on CHB.17Polaris Observatory CollaboratorsGlobal prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.Lancet Gastroenterol Hepatol. 2018; 3: 383-403Abstract Full Text Full Text PDF PubMed Scopus (1051) Google Scholar They estimated that the global prevalence of hepatitis B surface antigen in 2016 was 3.9%, corresponding to approximately 292 million cases. An estimated 10% (29 million) of these individuals have been diagnosed and only 5% of eligible patients have received antiviral treatment. In addition, 96% of CHB cases are found in low- and middle-income countries, with 65% being reported from Africa and the Western Pacific regions.30Sohn E. The global fight against hepatitis B is benefitting some parts of the world more than others.Nature. 2022; 603: S58-S59Crossref PubMed Google Scholar, 31Tian F. Feld J.J. Feng Z. et al.Feasibility of hepatitis B elimination in high-income countries with ongoing immigration.J Hepatol. 2022; 77: 947-956Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 32Stockdale A.J. Meiring J.E. Shawa I.T. et al.Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi.J Infect Dis. 2022; 226: 871-880Crossref PubMed Scopus (3) Google Scholar This may be related to lower rates of vaccinations and treatment in these regions. For example, in Africa, only 8% of infants receive their first dose of the hepatitis B vaccine within 24 hours of birth.32Stockdale A.J. Meiring J.E. Shawa I.T. et al.Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi.J Infect Dis. 2022; 226: 871-880Crossref PubMed Scopus (3) Google Scholar These data provide support for targeted efforts that must be undertaken to focus on the regions with the highest burden of CHB to prevent, diagnose, and treat this important cause of CLD.30Sohn E. The global fight against hepatitis B is benefitting some parts of the world more than others.Nature. 2022; 603: S58-S59Crossref PubMed Google Scholar, 31Tian F. Feld J.J. Feng Z. et al.Feasibility of hepatitis B elimination in high-income countries with ongoing immigration.J Hepatol. 2022; 77: 947-956Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 32Stockdale A.J. Meiring J.E. Shawa I.T. et al.Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi.J Infect Dis. 2022; 226: 871-880Crossref PubMed Scopus (3) Google Scholar On a positive note, it is estimated that more than 80 countries will achieve the target to reduce hepatitis B prevalence in children younger than age 5 years to less than 5% by 2030. On the other hand, areas with the highest prevalence are not projected to reach the set targets before 2050.25Cui F. Blach S. Manzengo Mingiedi C. et al.Global reporting of progress towards elimination of hepatitis B and hepatitis C.Lancet Gastroenterol Hepatol. 2023; 8: 332-342Abstract Full Text Full Text PDF PubMed Google Scholar In addition to viral hepatitis, ALD is a major cause of CLD worldwide.6World Health OrganizationEstimated mortality rate from cirrhosis and other chronic liver diseases.https://www.who.int/data/gho/indicator-metadata-registry/imr-details/1179Date accessed: December 13, 2022Google Scholar,7World Health Statistics.file:///C:/Users/User/Downloads/9789240051140-eng.pdfDate accessed: December 13, 2022Google Scholar Unlike CHC or CHB, which can be diagnosed through blood tests, the diagnosis of ALD relies on the self-reporting of alcohol consumption, which is fraught with problems.8Rehm J. Gmel Sr., G.E. Gmel G. et al.The relationship between different dimensions of alcohol use and the burden of disease-an update.Addiction. 2017; 112: 968-1001Crossref PubMed Scopus (593) Google Scholar In addition, given that alcohol consumption is associated with more than 200 diseases, estimates for ALD burden are difficult to quantify.8Rehm J. Gmel Sr., G.E. Gmel G. et al.The relationship between different dimensions of alcohol use and the burden of disease-an update.Addiction. 2017; 112: 968-1001Crossref PubMed Scopus (593) Google Scholar,9Rehm J. Imtiaz S. A narrative review of alcohol consumption as a risk factor for global burden of disease.Subst Abuse Treat Prev Policy. 2016; 11: 37Crossref PubMed Scopus (105) Google Scholar Furthermore, ALD may coexist with other liver diseases, especially with CHB or CHC, in which case, it is difficult to determine the primary driver for liver disease.10Messina J.P. Humphreys I. Flaxman A. et al.Global distribution and prevalence of hepatitis C virus genotypes.Hepatology. 2015; 61: 77-87Crossref PubMed Scopus (1173) Google Scholar,11Schwarzinger M. Baillot S. Yazdanpanah Y. et al.Alcohol use disorders and the burden of chronic hepatitis C in France, 2008-2013: a nationwide retrospective cohort study.J Hepatol. 2017; 67: 454-461Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Nonetheless , investigators using data from the WHO Global Status Report on Alcohol and Health have determined the burden of ALD.12Rehm J. Shield K.D. Global burden of alcohol use disorders and alcohol liver disease.Biomedicines. 2019; 7: 99Crossref PubMed Scopus (69) Google Scholar The report suggests that alcohol consumption caused almost half of the deaths attributed to CLD in 2016, and of 1,254,000 liver disease deaths, nearly 50% were estimated to be alcohol-attributable deaths (588,100; 95% CI, 531,700–683,400). Furthermore, 46.9% of all reported cases of CLD (95% CI, 42.4%–54.5%) were related to ALD. Finally, it is estimated that the highest DALY rates related to ALD were found in Eastern European, West African, and Central Asian countries.12Rehm J. Shield K.D. Global burden of alcohol use disorders and alcohol liver disease.Biomedicines. 2019; 7: 99Crossref PubMed Scopus (69) Google Scholar Although the GBD provides estimates for alcohol use and associated outcomes, it does not provide prevalence estimates of ALD. This is partially owing to a lack of accurate reporting and referral biases that limit the ability to estimate ALD incidence and prevalence. Nevertheless, GBD investigators have estimated that alcohol misuse is responsible for 27% of deaths from liver disease and 30% of liver cancer deaths worldwide.33GBD 2016 Alcohol CollaboratorsAlcohol use and burden for 195 countries and territories, 1990-2016: a syste